2023
DOI: 10.1021/acssynbio.2c00673
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In Silico Prediction and Mining of Exporters for Secretory Bioproduction of Terpenoids in Saccharomyces cerevisiae

Abstract: Terpenoids are the largest class of natural products, and their bioproduction by engineered cell factories receives high attention. However, excessive intracellular accumulation is one of the bottlenecks that limit the further improvement of the yield of terpenoid products. Therefore, it is important to mine exporters to achieve the secretory production of terpenoids. This study proposed a framework for the in silico prediction and mining of terpenoid exporters in Saccharomyces cerevisiae. Through the process … Show more

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Cited by 4 publications
(5 citation statements)
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“…The original strain, S. cerevisiae S6, was chosen because it had previously been modified to overproduce squalene by overexpressing the key rate-limiting enzymes that limit the MVA pathway’s rate of production, such as tHMG1 (truncated hydroxymethylglutaryl-CoA reductase), IDI (isopentenyl diphosphate delta-isomerase), and ERG20 (farnesyl pyrophosphate synthetase). First, OSC (oxidosqualene cyclase), AtLUP1 from Arabidopsis thaliana, was integrated into the genome of S6 to produce lupeol (Figure ).…”
Section: Resultsmentioning
confidence: 99%
“…The original strain, S. cerevisiae S6, was chosen because it had previously been modified to overproduce squalene by overexpressing the key rate-limiting enzymes that limit the MVA pathway’s rate of production, such as tHMG1 (truncated hydroxymethylglutaryl-CoA reductase), IDI (isopentenyl diphosphate delta-isomerase), and ERG20 (farnesyl pyrophosphate synthetase). First, OSC (oxidosqualene cyclase), AtLUP1 from Arabidopsis thaliana, was integrated into the genome of S6 to produce lupeol (Figure ).…”
Section: Resultsmentioning
confidence: 99%
“…As the transport is equilibrative, the compounds will not accumulate inside the cell. In case of toxicity, the yeast possesses a variety of ATP-driven ABC transporters for efficient multidrug efflux (Egner and Kuchler, 1996;Ortiz et al, 1997;Prasad and Goffeau, 2012;Liu et al, 2023).…”
Section: Discussionmentioning
confidence: 99%
“…The prevalence of promiscuous equilibrative transporters has significant implications for strain development in biotechnology. Transporter engineering has shown notable improvements in yeast cell factories for various compounds such as resveratrol (Pan et al, 2008;Vos et al, 2015), squalene (Liu et al, 2023), muconic acid (Pereira et al, 2019;Wang et al, 2021), and betaxanthin (Wang et al, 2021). Several reviews provide additional insights into this progress [see Kell et al (2015), Jezierska and Van Bogaert (2017), Kell (2018), van der Hoek and Borodina Belew et al (2022)].…”
Section: Discussionmentioning
confidence: 99%
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“…Lycopene’s high hydrophobicity means it accumulates within the cell membrane, which affects cellular function upon high-level production. Several studies have been emerging to resolve this issue via membrane engineering and two-phase extractive fermentation. Though in situ extraction of lycopene will help achieve a very competitive biotechnological process for lycopene production, the inability of the organic phase or the extractant to fully extract lycopene from the cellular membrane is the potential bottleneck. Thus, engineering the cell membrane for easy penetration of the extractant will resolve this menace.…”
Section: Introductionmentioning
confidence: 99%